Comparing Fracture Risk with Risedronate vs Alendronate During Drug Holidays

Data from a recent study is providing clinicians with insight into the fracture risk during osteoporosis drug holidays after long-term therapy with a pair of popular agents.

A propensity score-matched cohort study comparing the fracture risk during drug holidays after treatment with risedronate and alendronate, results of the study demonstrate drug holidays after long-term therapy with risedronate were associated with a small increase in risk of hip fracture compared with alendronate, but investigators note further research is needed to better understand risk mitigation.

“We found little difference in the association between risedronate versus alendronate drug holidays and hip fractures until approximately 2 years of not receiving therapy. Over 3 years, drug holidays after risedronate therapy were associated with an 18% relative and 0.6–percentage point absolute increased risk for hip fracture compared with alendronate drug holidays,” wrote investigators.

Funded by the Canadian Institutes of Health Research and citing a lack of direct comparisons between the agents, the current study was designed and led by a team of investigators representing multiple institutions in North America. To do so, investigators designed their study as a retrospective population-based, matched, cohort study using province-wide health care administrative databases detailing comprehensive coverage of Ontario residents aged 65 years or older from November 2000-March 2020.

The specific intent of the investigators’ efforts was to compare risks of drug holidays after long-term therapy with either agent, with long-term therapy defined as 3 years or more. The primary outcome of interest for the propensity score-matched analyses was hip fracture within 3 years after a 120-day ascertainment period. Investigators pointed out secondary analyses were planned to assess shorter follow-ups and sex-specific estimates.

The investigators' initial search identified 91,928 patients who received at least 3 years of continuous alendronate or risedronate therapy and had a subsequent drug holiday. After application of inclusion criteria, investigators identified 60,636 patients with at least 120 days of follow-up and without a history of hip or vertebral fracture for inclusion. The median age of this cohort at the start of the drug holiday was 80.2 (IQR, 10.3) years and 81% were women.

Of the 60,636 patients included in the study, 55% had long-term risedronate therapy and 45% had long-term alendronate therapy. Using propensity score-matching, 25,077 patients receiving alendronate were matched to 25,077 receiving risedronate, which yielded a cohort of 50,154 for inclusion in the final analyses.

Upon analysis, results suggested hip fractures rates were greater among risedronate than alendronate drug holidays, with event rates of 12.4 and 10.6 events per 1000 patient-years, respectively (HR, 1.18 [95% CI, 1.04-1.34]. Further analysis indicated this relationship became attenuated when any fracture was included as the outcome (HR, 1.07 [CI, 1.00-1.16]) and with shorter drug holidays (1 year: HR, 1.03 [CI, 0.85-1.24]; 2 years: HR, 1.14 [CI, 0.96-1.32]).

“We emphasize that our results do not indicate that alendronate therapy should be preferred over risedronate therapy. Indeed, several real-world studies identify little difference in fractures while treatment is received, with the exception of 2 of 5 secondary analyses that identified higher hip fracture risk after 3 years of therapy,” wrote investigators.

This study, “Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy,” was published in the Annals of Internal Medicine.